Conventional pharmaceutical dosage forms are well known and ubiquitous in the treatment of disease. This category includes the familiar pills, tablets, capsules, caplets, gel-caps, and other solid dosage forms that comprise the vast majority of pharmaceutical products on the market today.
However, not all of the products sold today are authentic. In recent years, there has been a significant increase in the number of false or counterfeit pharmaceutical goods in the marketplace. Direct-to-consumer marketing, global price competition, and Internet sales have all increased the likelihood that counterfeit pharmaceuticals may be produced or consumed anywhere in the world. It has been estimated that 10% of the pharmaceutical products sold globally are counterfeit, with substantially higher incidence among expensive medications or medications in high demand. (World Health Organization Fact Sheet No. 275, November 2003)
These counterfeit products generally imitate the external characteristics of the original products, such as size, shape, weight, color, or the presence of text or logos on the surface, using the same basic process technology as the originals. The resulting counterfeit pharmaceuticals may range from poor imitations with no active ingredient to products that contain related actives or wrong amounts of the correct active.
Efforts to defeat pharmaceutical counterfeiting thus far have focused on two main approaches. The first is the use of chemical markers or “taggants” in the dosage form that could be detected using sophisticated analytical techniques. The second is the use of radio frequency identification (RFID) technology on the product packaging to track and authenticate its identity throughout the supply chain, generating a “pedigree” for each product. (FDA Report, “Combating Counterfeit Drugs”, Feb. 18, 2004).
While these approaches hold promise in reducing the incidence of counterfeiting, they have foreseeable limitations. The chemical marker approach may be defeated by discovering the identity of the marker (through chemical analysis or other means) and adding it to counterfeit dosage forms. This is particularly true when the marker is added throughout the dosage forms, or uniformly to the surface of the dosage form, using common pharmaceutical processing techniques. Similarly, the RFID approach may be defeated by using electronic means to change or falsify the reading, transmission, or content of the electronic “pedigree”. Moreover, RFID techniques are not tied directly to the physical dosage forms, i.e.—a counterfeit product could exist within a package with proper RFID. Finally, these two strategies require the use of specific equipment or information to verify product identity. While they may work well for government and industry professionals along the supply chain, they do not offer any means of direct verification for the patient who ultimately uses the medication.
Hence, there is a need for additional dosage form attributes and related strategies that may further improve the ability to authenticate pharmaceutical products and deter counterfeiting efforts. Furthermore, it may be desirable that such strategies incorporate features that can be identified by the end user, the patient.
One approach to impart new attributes to pharmaceutical dosage forms is to use new process technology in their manufacture. Among the technologies that hold promise in this respect are the solid freeform fabrication (SFF) techniques, which use a layer-by-layer process sequence to assemble three-dimensional structures. These processes can create complex internal and external geometries by creating a different pattern as each “slice” of the structure is added.
One SFF process, three-dimensional printing (3DP), has particular utility for the creation of pharmaceutical dosage forms based on its ability to handle most active and inactive pharmaceutical ingredients. Although a variety of pharmaceutical dosage forms by 3DP have been disclosed in the art, no reference has been made to the problem of pharmaceutical counterfeiting or to structures or strategies that may serve to reduce or inhibit efforts at counterfeiting.